Emotion regulation is an essential component of mental health. Behavioral therapies have long acknowledged the importance of improving emotion regulation skills to promote resilience and to treat psychological disorders. Meditation is one mental training practice that has successfully been applied to cultivate skills in self-regulation of emotion, as it employs the un-biased present moment awareness of experiences. Several empirical studies have demonstrated that practice of meditation is associated with improvements in emotion regulation, mental health and well-being. However, little is known about the neurobiological mechanisms that underlie these improvements. The goal of this randomized, controlled, longitudinal study is to identify the neural mechanisms that underlie the improvements in emotion regulation associated with meditation practice. Ninety healthy but highly stressed participants will be randomly assigned to either an eight week Mindfulness-based stress reduction (MBSR) program or to an active control intervention that has been specifically designed to control for non-specific intervention effects associated with MBSR. In a pre-post design, participants will perform an emotion regulation task while functional MR images are acquired. We hypothesize that after the course, MBSR participants will show greater improvements in neural functions indicative of adaptive emotion regulation compared to participants of the control intervention. Furthermore, we will measure changes in gray matter morphometry in order to determine additional neural correlates of improved emotion regulation following MBSR. Our findings will help elucidate how meditation interventions exert their salubrious effects at the neurobiological level. PUBLIC HEALTH RELEVANCE: This study will identify neural mechanisms associated with changes in emotion regulation following participation in Mindfulness-Based Stress Reduction ("MBSR"). The data generated will provide important insights into how this intervention works to reduce stress and enhance well-being.